Expression of Bcl-2 family proteins in advanced laryngeal squamous cell carcinoma: Correlation with response to chemotherapy and organ preservation

被引:81
作者
Trask, DK
Wolf, GT
Bradford, CR
Fisher, SG
Devaney, K
Johnson, M
Singleton, T
Wicha, M
机构
[1] Univ Michigan, Med Ctr, Dept Otolaryngol Head & Neck Surg, Ann Arbor, MI 48109 USA
[2] Univ Michigan, Med Ctr, Dept Pathol, Ann Arbor, MI 48109 USA
[3] Univ Michigan, Med Ctr, Dept Internal Med, Ann Arbor, MI 48109 USA
[4] Loyola Univ, Dept Med, Chicago, IL 60611 USA
关键词
chemotherapy; organ preservation; apoptosis genes; Bcl-2;
D O I
10.1097/00005537-200204000-00009
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Objectives/Hypothesis: Induction chemotherapy and definitive radiation therapy in advanced laryngeal cancer has been shown to achieve survival rates that are similar to total laryngectomy and postoperative radiation therapy. In patients with advanced laryngeal cancer, quality of life can be significantly enhanced by treatment regimens that preserve the larynx. However, which patients will respond best to organ preservation protocols remains unknown. The Bcl-2 family proteins are involved in control of apoptosis and, potentially, tumor response to chemotherapy. Study Design: Retrospective analysis of immunohistochemical tumor characteristics and clinical outcome. Methods: To determine whether Bcl-2 family proteins were predictive of successful organ preservation, immunohistochemical analysis of tissue specimens from 47 patients with advanced laryngeal cancer from the U.S. Department of Veterans Affairs Cooperative Study Program (VA CSP-268) were evaluated for the expression of Bcl-2, Bcl-X-L, and Bax protein expression. Tumor response was classified as either complete or partial/nonresponse after induction chemotherapy. Protein expression was correlated with tumor response, organ preservation, and overall patient survival. Results: The Bcl-2 protein was expressed at high levels in only 15%, of specimens, but five of seven tumors with high Bcl-2 showed complete response (P = .10). The majority of tumors expressed high levels of Bel-X-L (74%). Reduced expression of Bcl-X-L was associated with a complete response (P = .143) and with larynx preservation (P = .06). Most patients (81%) had increased levels of Bax expression. Reduced expression of Bax was associated with a complete response rate (P = .074), but there was no correlation between Bax expression and larynx preservation. Conclusions: The findings indicate that laryngeal cancer cells typically produce high levels of only one of the apoptosis protective proteins, Bcl-2 or Bcl-X-L Prospective studies of larger numbers of patients are under way to determine whether Bcl-X-L expression will be a useful marker predicting larynx preservation.
引用
收藏
页码:638 / 644
页数:7
相关论文
共 39 条
  • [1] ASHKTORAB H, 1999, P AM ASS CANC RES LI, P190
  • [2] Overexpression of the death-promoting gene bax-alpha which is downregulated in breast cancer restores sensitivity to different apoptotic stimuli and reduces tumor growth in SCID mice
    Bargou, RC
    Wagener, C
    Bommert, K
    Mapara, MY
    Daniel, PT
    Arnold, W
    Dietel, M
    Guski, H
    Feller, A
    Royer, HD
    Dorken, B
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1996, 97 (11) : 2651 - 2659
  • [3] Bcl-2 inhibits p53 nuclear import following DNA damage
    Beham, A
    Marin, MC
    Fernandez, A
    Herrmann, J
    Brisbay, S
    Tari, AM
    LopezBerestein, G
    Lozano, G
    Sarkiss, M
    McDonnell, TJ
    [J]. ONCOGENE, 1997, 15 (23) : 2767 - 2772
  • [4] BCL-X, A BCL-2-RELATED GENE THAT FUNCTIONS AS A DOMINANT REGULATOR OF APOPTOTIC CELL-DEATH
    BOISE, LH
    GONZALEZGARCIA, M
    POSTEMA, CE
    DING, LY
    LINDSTEN, T
    TURKA, LA
    MAO, XH
    NUNEZ, G
    THOMPSON, CB
    [J]. CELL, 1993, 74 (04) : 597 - 608
  • [5] Bradford CR, 1997, ARCH OTOLARYNGOL, V123, P605
  • [6] OVEREXPRESSION OF P53 PREDICTS ORGAN PRESERVATION USING INDUCTION CHEMOTHERAPY AND RADIATION IN PATIENTS WITH ADVANCED LARYNGEAL-CANCER
    BRADFORD, CR
    ZHU, SB
    WOLF, GT
    POORE, J
    FISHER, SG
    BEALS, T
    MCCLATCHEY, KD
    CAREY, TE
    HONG, WK
    URBA, S
    ENDICOTT, JW
    CLOSE, L
    FISHER, SR
    TOOHILL, RJ
    KARP, D
    MILLER, DM
    CHEUNG, NK
    WEAVER, A
    HILLEL, AD
    SPAULDING, M
    CHANG, BK
    DOUGHERTY, B
    DECONTI, R
    GAREWAL, H
    FYE, C
    [J]. OTOLARYNGOLOGY-HEAD AND NECK SURGERY, 1995, 113 (04) : 408 - 412
  • [7] CAMPOS L, 1993, BLOOD, V81, P3091
  • [8] DOLE M, 1994, CANCER RES, V54, P3253
  • [9] DOLE MG, 1995, CANCER RES, V55, P2576
  • [10] Friedman M, 1997, ANN OTO RHINOL LARYN, V106, P445